I joined the Kondrashov lab in October 2010 as an EMBO Long-Term Fellow and currently hold an EU co-funded interdisciplinary postdoctoral (INTERPOD) fellowship, dividing my time between the labs of Fyodor Kondrashov and Ben Lehner. Before moving to Barcelona, I did my PhD (2006-2010) with Laurence Hurst at the University of Bath in the UK.
At Bath, our work helped to reveal that, from bacteria to mammals, protein-coding sequences evolve under multiple layers of selective constraint. Rather than just reflecting the functional/structural constraints that act on the final protein product, coding regions are also under selection to ensure proper processing at all stages of the protein production line, with signals embedded in the coding sequence contributing to adequate chromatin organization, specifying exonic splicing enhancers, and facilitating error-free translation.
My current research is focused on two major themes:
A. What is the evolutionary significance of erroneous gene expression?
Even in perfectly healthy cells, things go wrong on a regular basis. Ribosomes slip up during translation, polymerases initiate transcription at a cryptic start site, proteins interact with the wrong partners. I am interested in the consequences of erroneous genes expression in terms of the physiological effects they have on the cell (toxicity of protein aggregates, etc.) but particularly in the longer-term evolutionary implications. How do individual genes evolve to avoid or mitigate errors? What determines the fidelity of the different molecular machines involved in gene expression? And how do dedicated error-handling molecules like chaperones affect evolutionary dynamics on a genome-wide scale? Understanding how sequences and cellular systems are more or less well adapted requires, first and foremost, a quantitative empirical characterization of error processes. Consequently, mining high-throughput gene expression data (which is becoming increasingly comprehensive so that even very rare events can be captured) and molecular interaction data is a critical aspect of my work.
B. How do structural DNA-binding proteins affect sequence evolution?
Different parts of the genome evolve at different rates. Part of that variability appears to be linked to chromatin organization. For example, nucleosomal and nucleosome-free DNA in yeast and other eukaryotes evolve at different rates. I am interested in understanding the origins this relationship and more precisely characterizing the link between sequence variability in natural populations and the presence of histones and other DNA binding proteins. This involves exploiting genome-wide Chip-Seq and polymorphism data to disentangle the action of selection, for example for adequate nucleosome positioning, and biased mutability and repair associated with protein binding.
- Warnecke T, Becker EA, Facciotti MT, Nislow C, Lehner B (in press) Conserved substitution patterns around nucleosome footprints in eukaryotes and archaea derive from frequent nucleosome repositioning through evolution. PLoS Computational Biology Email me for the pre-print PDF
- Woods S, Coghlan A, Rivers D*, Warnecke T*, Jeffries SJ, Kwon T, Rogers A, Hurst LD, Ahringer J (2013) Duplication and retention biases of essential and non-essential genes revealed by systematic knockdown analyses. PLoS Genetics 9(5):e1003330
- Warnecke T, Supek F, Lehner B (2012) Nucleoid-associated proteins affect mutation dynamics in E. coli in a growth phase-specific manner. PLoS Computational Biology 8(12):e1002846
- Warnecke T (2012) Loss of the DnaK-DnaJ-GrpE chaperone system among the Aquificales. Molecular Biology and Evolution 29(11):3485-3495
- Warnecke T & Hurst LD (2011) Error prevention and mitigation as forces in the evolution of genes and genomes. Nature Reviews Genetics 12:875-881
- Warnecke T & Rocha EPC (2011) Function-specific accelerations in rates of sequence evolution suggest predictable epistatic responses to reduced effective population size. Molecular Biology and Evolution 28(8):2339-2349
- Warnecke T, Huang Y, Przytycka TM, Hurst LD (2010) Unique cost dynamics elucidate the role of frame-shifting errors in promoting translational robustness. Genome Biology and Evolution 2:636-645
- Warnecke T & Hurst LD (2010) GroEL dependency affects codon usage - support for a critical role of misfolding in gene evolution. Molecular Systems Biology 6:340
- Warnecke T, Guang-Zhong W, Lercher MJ, Hurst LD (2009) Does negative auto-regulation increase gene duplicability? BMC Evolutionary Biology 9:193
- Warnecke T, Weber CC, Hurst LD (2009) Why there is more to protein evolution than protein function: splicing, nucleosomes and dual-coding sequence. Biochemical Society Transactions 37(4):756-761
- Warnecke T, Batada NN, Hurst LD (2008) The impact of the nucleosome code on coding sequence evolution in yeast. PLoS Genetics 4(11):e1000250.
- Warnecke T, Parmley JL, Hurst LD (2008) Finding exonic islands in a sea of non-coding sequence: splicing related constraints on protein composition and evolution are common in intron-rich genomes. Genome Biology 9:R29
- Warnecke T & Hurst LD (2007) Evidence for a Trade-Off between Translational Efficiency and Splicing Regulation in Determining Synonymous Codon Usage in Drosophila melanogaster. Molecular Biology and Evolution 24(12):2755–2762